Scientific Theme: Advanced Modeling and Observing Systems

Complementary Research: Faculty Fellows Research
CIRES Aerosol Studies Have Led to Important Applications to Problems in World Health
Robert E. Sievers
(with Steve Cape, Chad Braun, Jessica Burger, David McAdams, Jessica
Best, Akiko Komura and Nicolette Wolters)
Funding: Aktiv-Dry L.L.C.
Studies of atmospheric aerosols by the Sievers group led to new methods of synthesizing
aerosol microparticles. This methodology for processing was patented in 1996 and has been
applied subsequently by several pharmaceutical companies and vaccine scientists. The
process consists of stabilizing microparticles of vaccines and pharmaceuticals then drying
and micronizing them.
Accomplishments
Aerosol scientists, physicians, immunologists, formulation experts, engineers, device designers, and others are
working together to make a stable, inhalable vaccine to reduce deaths from measles (now ca. 1,000 per day).
Because of its expertise in aerosol science, CIRES has been invited to play a leadership role in an international
collaboration to develop an inhalable powder of live attenuated measles vaccine to be manufactured by the Serum
Institute of India (SII). Development through Phase I human trials is being funded by a grant from Aktiv-Dry LLC
as part of the Grand Challenges in Global Health initiative. The inhalable vaccine is being developed specifically for
the developing world, with due consideration given to thermal stability, cost, ease of needle-free administration, and
shipping volume and weight. Methods: Vaccine was supplied by SII (Pune, India). Candidate live and placebo
formulations were dried from aqueous suspension to inhalable powder using the CIRES-patented process Carbon
Dioxide Assisted Nebulization with a Bubble Dryer ® (CAN-BD). Powder characterization included live-vaccine
virus activity, moisture content, powder particle aerodynamic diameter after dispersal. An inexpensive active drypowder
inhaler is also under development; two patent applications have been filed by CIRES scientists, Bob Sievers,
Steve Cape and Jessica Best. Results: Formulation with myo-inositol, gelatin, and L-arginine as the major
constituents and CAN-BD drying yielded amorphous powders with 75%±16% retained activity (95% confidence
interval), thermal stability that passed the WHO 7-day 37°C test, low moisture content of only 0.7 to 1.2%, and a
mass-median aerodynamic diameter of 3 µm. Conclusions: The SII measles vaccine can be processed at 50°C into
an inhalable dry powder with the
CAN-BD process, with activity
retention through processing
similar to present commercial
lyophilization, and short-term
stability, meeting WHO
requirements. If proven safe and
effective, and introduced
successfully into developing
countries, WHO expects the
demand for this inhaled aerosol
vaccine to be 300,000,000 doses
per year, and save many
thousands of lives.
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Photo of new Dry Powder
Inhaler (DPI) to deliver aerosols
of vaccines to 1 to 5-year-old
children.